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Control of Stereoselectivity in Diverse Hapalindole Metabolites is Mediated by Cofactor‐Induced Combinatorial Pairing of Stig Cyclases
Author(s) -
Li Shasha,
Newmister Sean A.,
Lowell Andrew N.,
Zi Jiachen,
Chappell Callie R.,
Yu Fengan,
Hohlman Robert M.,
Orjala Jimmy,
Williams Robert M.,
Sherman David H.
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201913686
Subject(s) - stereospecificity , chemistry , stereochemistry , stereoselectivity , electrophile , pairing , cofactor , combinatorial chemistry , biochemistry , enzyme , catalysis , physics , superconductivity , quantum mechanics
Stereospecific polycyclic core formation of hapalindoles and fischerindoles is controlled by Stig cyclases through a three‐step cascade involving Cope rearrangement, 6‐ exo ‐trig cyclization, and a final electrophilic aromatic substitution. Reported here is a comprehensive study of all currently annotated Stig cyclases, revealing that these proteins can assemble into heteromeric complexes, induced by Ca 2+ , to cooperatively control the stereochemistry of hapalindole natural products.